Abstract

Caspase inhibition has been demonstrated to be therapeutically effective in moderating excessive programmed cell death, or apoptosis. Publications detailing programs in the pharmaceutical industry have been more frequent in recent years, ranging from SAR studies to clinically relevant animal models of disease. A summary of the work published in this exciting new area is presented, outlining the broad applicability of this fundamental cellular mechanism across several disease indications. This area of research has matured to the level of advancing compounds into clinical trials: VX-74 (Pralnacasan) and VX-765 as anti-inflammatory agents, and IDN-6556, a pancaspase inhibitor as an anti-apoptotic agent.

Keywords: Caspase inhibitor, apoptosis, ICE, VX-740, VX-765, IDN-6556, a-Fas-induced liver model, Jurkat, peptidomimetics